PROTACs:癌症药物发现和开发的新策略
Xin Han1,2,3,4, Yi Sun1,2,3,4,5
1Cancer Institute (Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education) of the Second Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of Medicine Hangzhou China.
MedComm
|June 1, 2023
概括
解向嵌合体 (PROTAC) 技术为药物发现提供了一个有前途的方法. 本综述强调了RING型E3酶招募器,这对于推进向蛋白质降解疗法至关重要,特别是在癌症药物开发中.
科学领域:
- 生物化学 生物化学
- 药用化学 医学化学
- 在瘤学瘤学.
背景情况:
- 蛋白质溶解向嵌合体 (PROTAC) 技术是药物发现的重大进步,使得向以前无法向的蛋白质成为可能.
- PROTACs利用一个三元复杂机制,涉及一个蛋白结合剂,一个E3酶结合体和一个链接器.
- 临床试验已经表明PROTAC降解剂在抗癌疗法中的潜力,但E3酶招募剂的有限可用性阻碍了更广泛的应用.
研究的目的:
- 审查现有的RING型E3泛素酶及其在PROTAC技术中用作E3联体的小分子招募剂.
- 讨论这些E3配体在抗癌药物发现中的应用.
- 确定迫切需要新型E3酶招募剂,以扩大向蛋白质降解 (TPD) 的范围.
主要方法:
- 文献综述总结了已确立的RING型E3无素连接酶.
- 对这些E3结合酶的小分子招募剂的分析.
- 检查PROTAC在使用这些E3配体的抗癌药物发现中的应用.
主要成果:
- 目前可用的RING型E3泛素酶及其相应的小分子招募剂的识别和摘要.
- 这些E3配体在用于癌症治疗的PROTAC介导向蛋白质降解中的成功应用概述.
- 突出了尽管在人类基因组中编码了大量的E3酶,但各种E3酶招募器的稀缺性.
结论:
- 限定的E3酶招募器是PROTAC技术和向蛋白质降解 (TPD) 的一个主要瓶.
- 环型E3链酶及其招募剂是开发新型PROTAC的关键领域.
- 这一综述为未来的研究提供了宝贵的参考,旨在发现和开发用于癌症药物发现的高效E3配体.
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